U.S. patent application number 10/570689 was filed with the patent office on 2007-02-08 for pharmaceutical combination preparation containing glycyrrhizine, zinc, and a compound comprising a thiol group or a group that is metabolized thereto.
Invention is credited to Dana Flavin-Koenig.
Application Number | 20070031510 10/570689 |
Document ID | / |
Family ID | 34223349 |
Filed Date | 2007-02-08 |
United States Patent
Application |
20070031510 |
Kind Code |
A1 |
Flavin-Koenig; Dana |
February 8, 2007 |
Pharmaceutical combination preparation containing glycyrrhizine,
zinc, and a compound comprising a thiol group or a group that is
metabolized thereto
Abstract
The invention relates to the application of a combination
including all forms of zinc at least one for the orally applied
combination of a free thiol group or a group that is metabolized to
a free thiol in a mammal, and as a the only pure plant part,
glycyrrhicinic acid or the substance from succus liquiritiae for
the production of a medication to fight acute or chronic viral
infections.
Inventors: |
Flavin-Koenig; Dana;
(Greenwich, CT) |
Correspondence
Address: |
ROBERTS, MLOTKOWSKI & HOBBES
P. O. BOX 10064
MCLEAN
VA
22102-8064
US
|
Family ID: |
34223349 |
Appl. No.: |
10/570689 |
Filed: |
September 3, 2004 |
PCT Filed: |
September 3, 2004 |
PCT NO: |
PCT/EP04/09814 |
371 Date: |
March 6, 2006 |
Current U.S.
Class: |
424/643 ;
424/703; 424/757; 514/26; 514/440; 514/562 |
Current CPC
Class: |
Y02A 50/30 20180101;
A61K 31/704 20130101; A61P 31/16 20180101; A61K 31/7016 20130101;
A61K 33/30 20130101; A23L 33/15 20160801; A61P 11/00 20180101; Y02A
50/463 20180101; A61K 31/198 20130101; A61P 31/22 20180101; A23V
2002/00 20130101; A61P 31/12 20180101; A23L 33/105 20160801; A61K
36/484 20130101; A61K 31/198 20130101; A61K 2300/00 20130101; A61K
31/7016 20130101; A61K 2300/00 20130101; A61K 31/704 20130101; A61K
2300/00 20130101; A61K 33/30 20130101; A61K 2300/00 20130101; A61K
36/484 20130101; A61K 2300/00 20130101; A23V 2002/00 20130101; A23V
2250/252 20130101; A23V 2250/1642 20130101 |
Class at
Publication: |
424/643 ;
424/757; 514/440; 514/562; 424/703; 514/026 |
International
Class: |
A61K 36/48 20060101
A61K036/48; A61K 33/32 20060101 A61K033/32; A61K 33/04 20060101
A61K033/04; A61K 31/198 20070101 A61K031/198; A61K 31/385 20060101
A61K031/385; A61K 31/704 20070101 A61K031/704 |
Foreign Application Data
Date |
Code |
Application Number |
Sep 4, 2003 |
DE |
103 40 845.2 |
Claims
1. Application of a combination comprising Zinc substances, at
least one of the orally taken thiol substances with at least one
free thiol group or a group which sets a thiol free when
metabolized in a mammal, as the only pure plant substance
glycyrrhicinic acid or the substance from succus liquiritiae, for
the production of a medication to fight acute or chronic viral
infections.
2. Application according to claim 1, characterized in that the
components even in separate application units are arranged together
inside of one package.
3. Application according to claim 1, characterized in that two of
the three components are combined in a single substance.
4. Application according to claim 1, characterized in that all
three components are together in a single combined substance.
5. Application according to claim 1, characterized in that the
combination of at least one free thiol group, or a group that is
metabolized in mammals to a free thiol is out of N-acetylcysteine,
Methionine, cysteine, allylcysteine, alpha lipoic acid, or
sulfur.
6. Application according to claim 1, characterized in that the
glycyrrhicinic acid is in the form of succus liquiritiae.
7. Application according to claim 1, characterized in that it
further includes one or more pharmaceutical applied non active
ingredients.
8. Application according to claim 1, wherein the acute or chronic
viral infections includes virus infections with corona virus, rhino
virus, coxsackie virus, influenza A- and B-viruses, Herpes viruses,
cytomegalo viruses, Hepatitis A- and B- and C-Viruses,
Epstein-Barr-virus, and other colds or flu viruses.
9. Application according to claim 1, characterized in that it
applies to virus diseases and diseases of the upper respiratory
tract.
10. Application according to claim 1, characterized in that the
glycyrrhinicic acid be applied in a daily doses of 750 mg to 2000
mg, that the zinc be applied in a daily doses from 50 mg to 150 mg
(in relation to the element zinc only) and the combination of at
least one free thiol group or a group that is metabolized to a free
thiol in a mammal, in a daily doses from 600 mg to 2400 mg.
11. Application according to claim 10, characterized in that the
daily doses is divided into at least two single doses.
12. Application according to claim 2, characterized in that the
combination of at least one free thiol group, or a group that is
metabolized in mammals to a free thiol is out of N-acetylcysteine,
Methionine, cysteine, allylcysteine, alpha lipoic acid, or
sulfur.
13. Application according to claim 3, characterized in that the
combination of at least one free thiol group, or a group that is
metabolized in mammals to a free thiol is out of N-acetylcysteine,
Methionine, cysteine, allylcysteine, alpha lipoic acid, or
sulfur.
14. Application according to claim 4, characterized in that the
combination of at least one free thiol group, or a group that is
metabolized in mammals to a free thiol is out of N-acetylcysteine,
Methionine, cysteine, allylcysteine, alpha lipoic acid, or
sulfur.
15. Application according to claim 6, characterized in that it
further includes one or more pharmaceutical applied non active
ingredients.
16. Application according to claim 7, wherein the acute or chronic
viral infections includes virus infections with corona virus, rhino
virus, coxsackie virus, influenza A- and B-viruses, Herpes viruses,
cytomegalo viruses, Hepatitis A- and B- and C-Viruses,
Epstein-Barr-virus, and other colds or flu viruses.
17. Application according to claim 8, characterized in that it
applies to virus diseases and diseases of the upper respiratory
tract.
18. Application according to claim 9, characterized in that the
glycyrrhinicic acid be applied in a daily doses of 750 mg to 2000
mg, that the zinc be applied in a daily doses from 50 mg to 150 mg
(in relation to the element zinc only) and the combination of at
least one free thiol group or a group that is metabolized to a free
thiol in a mammal, in a daily doses from 600 mg to 2400 mg.
Description
[0001] The invention consists of a pharmaceutical or Nutrient
combination preparation, of glycyrrhicinic acid, zinc and an orally
acceptable connection to a free thiol group or a group that can be
metabolized to a thiol group in a mammal's body. The invention
further relates to a use for application for fighting viral
infections especially Flu types of viruses.
[0002] Glycyrrhicinic acid (or glycyrrhicin) is an integral part of
the root of Glycyrrhizia glabra LINNE (commonly called Licorice)
with the following structural formula: ##STR1##
[0003] The natural, unpeeled dried root of glycyrrhiqia glabra is
known as licorice root, and used as a medication in the natural
healing arts. Liquid and solid forms for oral intake are known as
succus liquiritiae. Licorice is made of such succus liquiritiae
with a concentration of glycyrrhicinic acid of more than 1%. In
Natural medicine, licorice root is used for catarrh, in the upper
airways, and ulcers in the stomach and duodenum. In catarrh the
expectorant, mucolytic and anti-inflammatory actions of the
medication are most known.
[0004] In animal studies, glycyrrhicinic acid has shown an
interferon inducing effect, connected to an antiviral effect. It
also shall have a direct antiviral effect. Zinc is also known as a
trace element that is imperative for the Immune system. In cases of
viral infection, when zinc is taken, it increases the interferon
activity to a multiple. In addition, zinc has a direct antiviral
activity on the viral replication.
[0005] Thiol containing substances have many therapeutic
acitivities. In connection to this invention, it is especially
meaningful that thiol groups increase the number of antiviral
functioning lymphocytes, e.g. the Th-1 lymphocytes and natural
killer cells which are the sources for interferon especially
interferon alpha and interferon gamma. The increase in the number
of functioning competent immune cells is the result of the binding
of the thiol group to nitric oxide. The concentration of nitric
oxide (NO) is elevated in viral infections and responsible for the
immobilization of the antiviral lymphocytes, which weakens the
natural endogenous defense against viral infections.
[0006] In Japan there is a combination preparation of
glycyrrhicinic acid, glycine and cysteine on the market to treat
chronic viral hepatitis and post hepatic liver cirrhosis. The
purpose of the invention is to create a synergistic antiviral
activity that is greater than one would expect from an application
of the individual components.
[0007] This purpose is met through the composition according to
claim 1 and the usage according to claim 8.
[0008] The inventor surprisingly discovered the combination of
glycyrrhicinic acid, zinc and a thiol containing group, or
metabolized to a thiol containing group had an astounding antiviral
activity.
[0009] The combination of substances can be in the form of three
separate preparations, in a single package. It could also be any
two of the substances worked into one combined substance. Further
all three substances could be formed together into one combination
substance.
[0010] Glycyrrhicinic acid is preferentially applied in the
invention in the form of succus liquiritiae. Succus liquiritiae can
be a liquid or a dried powder, which as mentioned above is obtained
from the licorice root. A preferable succus liquiritiae liquid
contains 5% glycyrrhicinic acid (50 mg/ml)
[0011] The oral dose of glycyrrhicinic acid is preferably 1500 mg
to 2000 mg per day for adults. It is preferred to be given in two
or three doses per day, especially preferred in three doses.
[0012] Zinc can be used in all typical pharmaceutical acceptable
forms, including zinc orotate, zinc aspartate, zinc histidine, zinc
sulfate, for the combination preparation according to the
invention. The preferred oral dose for adults is 75 mg to 150 mg
per day (referring to the element zinc). The daily dosage of zinc
is also preferred to be portioned, e.g. three times a day.
[0013] The oral application of a free thiol group or a group that
is metabolized to a free thiol group in mammals is chosen preferred
from N-acetylcysteine, Methionine, Cysteine, allylcysteine, alpha
liponic acid and Sulfur. Especially preferred is N-acetylcysteine,
as this has also a mucolytic activity. All available preparations
presently on the market are suitable including but not exclusively,
ACC.RTM. from Hexal, Fluimucil.RTM. from Zambon etc.
[0014] This group of thiol containing substances is preferred at
the doses of 1200 mg to 2400 mg for adults preferentially applied
in divided doses per day, eg. three divided doses.
[0015] The daily doses of the individual substances for children is
preferentially half of the adult doses.
[0016] The inventions combination preparation may contain
additional pharmaceutical substances eg. paracetamol or acetyl
salicylic acid.
[0017] The active substances of the inventions combination
preparation is preferentially for oral application, although a
parenteral, topical, intranasal, intravaginal and rectal
application is not ruled out. Oral application forms include
tablet, capsule, pill, buccal tablet, elixir, suspensions, syrups
and similar forms. These application forms can include appropriate
carriers eg dicalsium phosphate, binders such as gums, including
gum arabicum, corn starch, or gelatine, breakdown products such as
corn starch, potato starch, and Alginin acid, lubricants, such as
magnesium stearate, sweetening substances, taste enhancers and all
other commonly used enhancing and support subtances used in the
pharmaceutical industry.
[0018] The invention combination preparation is for fighting acute
and chronic, preferentially acute, virus infections for example,
but not limited to corona viruses, rhino viruses, coxsackie
viruses, Influenza A- and B-viruses, Herpses viruses,
cytomegaloviruses, hepatitis A-, B- and C-viruses,
Epstein-Barr-virus, and other viruses causing colds and all flu
infections. This is especially applicable to infections of the
upper respiratory tract.
[0019] It was surprisingly found that the combination preparation
of the above three substances had an astounding synergistic
activity.
[0020] In clinical studies each single substance was tested in flu
symptoms (colds, flu, viral infection of the upper respiratory
tract) whose duration without treatment normal lasted 7 days.
[0021] The results obtained were:
[0022] a) Zinc as a single treatment: [0023] 125mg per day, divided
in three doses:
[0024] Slight lessoning of the duration of the illness to an
average of 5 days.
[0025] On a scale of 1-10 (1 least effect, 10 maximum effect):2
[0026] b) N-Acetylcysteine [0027] 2400 mg, divided in three
doses;
[0028] Moderate reduction of duration of illness to an average of 4
days.
[0029] On a scale of 1-10 (1 least effect, 10 maximum effect):5
[0030] c) Glycyrrhinic acid [0031] 1500 mg, divided in three
doses;
[0032] Considerable reduction in the duration of illness to an
average of 2.5 days;
[0033] On a scale of 1-10 (1 least effect, 10 maximum effect):7
[0034] The average duration of illness with the treatment
combination of all three of the above substances a), b), and c) in
the majority of the cases the duration of the illness was shortened
to 24 hours or less. Exactly said: 30 Adults (Men and women) had an
improvement in symptoms (decreasing tiredness and maliase) already
after 30 to 60 minutes after taking the first dose of combination
of a), b), and c). 24 hours later, 85% of the patients were
completely without symptoms and able to return to work. The maximum
duration in a few cases lasted 5 days.
[0035] 90% of the patients stayed healthy. 10% of the patients who
did not follow the suggestions to avoid alcohol and to have a full
nights sleep, showed new symptoms which however after taking the
treatment again quickly subsided.
[0036] Furtheron, 20 children between the ages of 7 to 15 years old
were treated with half of the doses from the combination of a) b)
and c). The results were the same as by the adults. That is, after
30 to 60 minutes a significant improvement of the symptoms was seen
and after 24 hours, most of the children were completely without
signs of illness so that they could return to school the next
day.
[0037] This surprising synergy of the combination of the above
three substances a), b) and c) was not to be expected. It was known
for some time that glycyrrhicinic acid had antiviral activity, but
the incredible enhancement of activity with zinc and thiols that
lead to an extraordinary increase in the elimination of symptoms
was not discovered before the development of the combination
therapy.
[0038] The preparation in the invention is not only useful for
those ill, but of great use also for the economy in that the
symptoms of diseases causing inability to work (colds, flu's) can
be eliminated in a short period of time. Side effects in the short
duration of therapy are not observed.
[0039] The following examples elucidate the invention further:
EXAMPLES
[0040] In all examples the application of the combined individual
doses was 500 mg glycyrrhinic acid (or about 10 ml (a small
tablespoon) succus liquiritiae depuratus solutus 1+1 from the
company Dr. Hetterich GmbH & Co. KG, Fuerth, Bavaria), 50 mg
Zinc (as an element in the form of zinc orotate) and 800 mg
N-Acetylcysteine. Patients with high fevers (above 38.5.degree. C.)
were given paracetamol in addition to the treatment to decrease the
fever. (Slight fevers did not require any special treatment)
Example 1
[0041] A 12 year old girl presented with low grade fever, lethargy,
tiredness, mylagia, sore throat, and general malaise following an
infection (Streptococcus negative.) She was treated with half of
the doses of the above combination and she showed improvement
within an hour. The application was repeated every 6 hours (except
for the night). In 24 hours she showed a general improvement and no
symptoms of any virus infection and was back in school.
Example 2
[0042] A 15 year old girl was presented with fever, runny nose,
watering eyes, sore throat, (Streptococcus negative) and mild
cough. She was treated with half of the doses of the above
combination. After 30 minutes the child felt better, with less
malaise and lethargy, the rest of the symptoms were milder. The
treatment was repeated twice after 6 hours, respectively. In 24
hours she had no symptoms. She preferred not to attend school but
to stay home and rest for one more day.
Example 3
[0043] A 16 year old boy presented with myalgie, fatigue, malaise,
lethargy and tiredness and fever (low grade). He was treated half
of the doses of the above combination. He showed improvement in 30
minutes with more energy and less lethargy. The treatment was
repeated every 6 hours (except for the night). The entire symptoms
were gone in 24 hours. The boy returned to school the next day.
Example 4
[0044] A 38 year old Woman, complained of fever, malaise, runny
nose, myalgia, lethargy, weakness and tiredness. She was given the
above combination dosage at 10 A.M.. Half an hour later she had
less symptoms, her lethargy was gone, but the general malaise was
still evident. She received two more treatments during the day and
by the next morning she could resume her daily activities without
hinderness. The symptoms were all gone.
Example 5
[0045] A 52 year old woman presented with flu-like symptoms of the
upper rispiratory, fever, headache, myalgia, tiredness, malaise and
lethargy. She was treated with the above dosage combination and
slept most of the day. Her symptoms were almost completely reduced
by the second day where to be on the safe side we resumed the
treatment twice on the second day. Symptoms were completely gone
after the second day.
Example 6
[0046] A 42 year old man presented with fever (low grade), malaise,
myalgia, sniffles, light cough and sore throat. He complained of
his flu symptoms and general weakness and tiredness. He was given
the above single dose of combined substances at 2: P.M. and slept
until evening when he received another single dose of combined
substances. The next moring he felt better and wanted to go to
work, however it was recommended he take another treatment for the
morning and at noon to insure that he did not have a relapse. He
returned to work the next day, feeling no more symptoms or illness
of any sort.
Example 7
[0047] A 58 year old man presented with flu like symptoms including
fever (low grade), malaise, tiredness, myalgia, headache and sore
throat. He was given the above combination in single dose three
times in the first day. After the first treatment in the morning
his symptoms of tiredness and malaise were reduced in 30 minutes,
he was however still weak and rested the entire day. The next day
he was more than 80% better but remained home the entire mornig,
returning to work in the afternoon.
Example 8
[0048] A 65 year old woman complained of upper rispiratory symptoms
including runny nose, sore throat, malaise, low grade fever, and
light cough. She was treated with the above combination in the
morning and rapidly felt better after 1 hour. She was however still
with a sore throat and myalgia. The treatment was repeated twice
that day and once in the following morning. Her illness was gone
after 36 hours.
* * * * *